The goal of the proposed research is to investigate the molecular population genetics underlying clinal variation at the human acid phosphatase locus (ACP1). Allele frequencies of this protein show a strong correlation with mean annual temperature among human populations, indicating the possible role of natural selection in shaping patterns of variability. We will evaluate this hypothesis by sequencing two portions of the ACP1 gene using a nested sampling design that incorporates both a global human diversity panel and individual population panels from different portions of the cline. Addressing variation of ACP1 at these scales we will be able to characterize the form and strength of selection operating on the locus, and also distinguish how these patterns vary over the cline in ACP1 variability. To date, we have very few examples of human genes that have evolved in response to different physical environments, despite the existence of numerous phenotypic traits that indicate that these challenges have played a strong role in shaping modern patterns of human diversity. With ACP1 we have the opportunity to fill this gap and to elucidate the molecular mechanisms underlying natural selection at this locus. [unreadable] [unreadable]